This is a grant for the support of the protein structure laboratory at Caltech. The main objective of this program is an understanding of the interactions between proteins, nucleic acids, and organic intercalating molecules as they are involved in biological control. Three specific projects are covered by this grant: 1. Lactose repressor/operator chemistry and crystallography. 2. Crystallography of small DNA molecules (4 to 10 base pairs) and their complexes with intercalating agents and other drugs. 3. Crystallography of prokaryotic and eukaryotic cytochromes c and cytochrome oxidase. Lac operator has been synthesized and cloned in plasmids, and a practical extraction method developed that yields 13 mg operator from 1 kg of E. coli. Repressor and operator have been cocrystallized, and x-ray analysis awaits only the growth of larger crystals. Crystallization trials of complexes of tetranucleotides CGCG, CCGG and others have been set up with bis-ethidium-spermine, cis-Pt(NH3)2Cl2, and other intercalating drugs. The single crystal structure analyses of CCGG and of high- and low-salt forms of CGCG are under way. Attempts are being made to crystallize two double-stranded DNA decamers. Tuna cytochrome c is in the final stages of refinement, and crystals for x-ray examination are being grown from Pseudomonas cytochrome oxidase (or nitrite reductase).